Papillomaviruses induce persistent epithelial lesions, known as papillomas. Genital papillomavirus infection is widespread and associated with the development of cervical cancer. The viral E2 proteins regulate viral transcription, replication and episomal genome maintenance. Our aim is to elucidate the mechanisms by which the E2 proteins control the viral life cycle. We have shown that papillomavirus genomes and the E2 transactivator protein interact with cellular mitotic chromosomes in dividing cells. This ensures that viral genomes are properly segregated to daughter cells and are retained within the nucleus. [unreadable] ?We have shown that there are variations in the association of different papillomavirus E2 proteins with mitotic chromosomes. We show that mitotic tethering is a common strategy among papillomaviruses but different viruses have evolved different chromosomal targets. [unreadable] ?We have shown that Brd4 is required for E2-mediated transcriptional activation but not genome partitioning of all papillomaviruses[unreadable] ?HPV16 DNA is often integrated in cancers, disrupting the E1 or E2 genes. We demonstrate that the E2 protein is primarily a transcriptional repressor when expressed from the virus. Furthermore, E2-mediated repression requires both the transactivation function of E2 and specific binding of the E2 protein to sites in the LCR. We find no evidence that the E1 protein directly modulates HPV16 gene expression. [unreadable] ?We have shown that the HPV8 E2 protein binds to distinct regions of mitotic chromosomes and does not require the Brd4 prrotein, as has been shown for BPV-1 E2.[unreadable]